Testing the Developmental Origins Hypothesis

INTRODUCTION: Growing evidence shows that reduced fetal growth rate is associated with adult cardiovascular risk markers (e.g., obesity) and disease, and evidence worldwide indicates that this relationship is independent of birthweight. The leading theory describes 'developmental programming' in utero leading to permanent alteration of the fetal genome. While those changes are adaptive in utero, they may be maladaptive postnatally. OBJECTIVE: To directly test, for the first time in humans, whether differential blood pressure (BP) control in pregnancy has developmental programming effects, independent of birthweight. We predict that, like famine or protein malnutrition, 'tight' (vs. 'less tight') control of maternal BP will be associated with fetal under-nutrition and effects will be consistent with developmental programming. METHODS: CHIPS-Child is a parallel, ancillary study to the CHIPS randomized controlled trial (RCT). CHIPS is designed to determine whether 'less tight' control \[target diastolic BP (dBP) 100mmHg\] or 'tight' control \[target dBP 85mmHg\] of non-proteinuric hypertension in pregnancy is better for the baby without increasing maternal risk. CHIPS-Child is a follow up study at 12 m corrected post-gestational age (± 2 m) limited to non-invasive examination \[anthropometry, hair cortisol, buccal swabs for epigenetic testing and a maternal questionnaire about infant feeding practices and background\]. Annual contact will be maintained in years 2-5 and contact will include annual parental measurement of the child's height, weight and waist circumference. Sample size:. CHIPS will recruit 1028 women. We estimate that 80% of CHIPS centres will participate in CHIPS-Child, approximately 97% of babies will survive, and 90% of children will be followed to 12 m resulting in a sample size of 626. Power will be \>80% to detect a between-group difference of ≥0.25 in 'change in z-score for weight' between birth and 12 m (2-sided alpha=0.05, SD 1).